PROJECT SUMMARY This 4-year K01 career development award was designed to provide the necessary resources and training to the candidate, Dr. Shilpa N Bhupathiraju, to launch an independent research career in the field of nutrition and chronic disease epidemiology. The training plan includes a mixture of didactic course work, hands-on laboratory training, metabolomics workshops, seminars, advisory committee meetings, career enrichment programs, and attendance at national conferences. It is intended to provide Dr. Bhupathiraju with the necessary skill set in the emerging fields of metabolomics and systems epidemiology. Dr. Bhupathiraju is a highly motivated and capable young researcher with an established record of research productivity in the area of dietary and lifestyle determinants of chronic diseases. However, in order to achieve research independence, she will need to master novel analytic tools in nutritional epidemiology such as systems epidemiology and metabolomics. The proposed project will be implemented at the Harvard T.H. Chan School of Public Health. The school is adjacent to a wide range of research and medical institutions giving Dr. Bhupathiraju access to an enormous range and depth of scientific expertise, resources, and opportunities to advance her career and establish research independence. The proposed project is unique and timely as it is the first ever to evaluate novel and unexplored metabolic biomarkers of type 2 diabetes (T2D) in a group of older Puerto Ricans. Among all Hispanic sub-groups, Puerto Ricans experience the poorest health with excessive prevalence of T2D, metabolic syndrome, hypertension, and obesity. They have unique dietary patterns that may contribute to T2D risk. Stored baseline samples from the Boston Puerto Rican Health Study will be used to measure promising metabolites related to T2D risk, including gut microbiota metabolites, urea cycle metabolites, 2-aminoadipic acid, 2-hydroxybutanoic acid, branched chain and aromatic amino acids, and ?-aminoisobutyric acid in an efficient case-control study design of 120 prevalent T2D cases and 120 matched controls. By taking advantage of already measured cardiometabolic biomarkers at baseline and 2-years, the project will also evaluate the cross-sectional and prospective associations between candidate metabolites and intermediate markers of T2D. Secondary to these aims, the candidate will also 1) identify pathways and signatures associated with T2D, and 2) examine dietary sources of key metabolites. The Boston Puerto Rican Health Study is well-suited to examine these research questions as it has stored biospecimens and well-validated measures of diet, lifestyle, and ethnic-specific variables such as acculturation and perceived stress. Findings from the proposed research may help identify novel biomarkers and prevention strategies for T2D. The world-class mentoring team who are leaders in their respective fields together with the rich scientific environment and resources will ensure the successful and seamless transition of Dr. Bhupathiraju into an independent investigator in nutrition, metabolomics, and chronic disease epidemiology.